During the past year we have transplanted, via the portal vein, dispersed hepatocytes prepared from heterozygous Gunn rat liver with adequate uridine diphosphate glucuronyl transferase (UDPGT) levels to jaundiced, homozygous Gunn rats lacking UDPGT, and effected a lowering of bilirubin in the latter rats. We have developed a model of acute liver failure in Lewis rats by administration of dimethylnitrosamine (DMNA), 20 mg/kg, which allows survival of less than 10% of the rats receiving no further treatment. Isologous hepatocytes, transplanted via the portal vein or into the peritoneal cavity one day after administration of DMNA increases the survival to greater than 60%. Transplanted hepatocytes are able to provide sufficient metabolic support to ensure survival and allow the host's own liver to regenerate. During the coming year we plan to transplant liver cells from heterozygous to homozygous Gunn rats and to correlate liver UDPGT levels with plasma bilirubin levels. We also plan to transplant liver cells from normal catalasemic to acatalasemic mice and observe the effect on blood and liver catalase levels of transplanted mice. Rats with DMNA induced acute liver failure will receive hepatocellular allografts and charcoal hemoperfusion will also be attempted in dogs with DMNA induced acute liver failure. BIBLIOGRAPHIC REFERENCES: Matas, A.J., Sutherland, D.E.R., Steffes, M.W., Simmons, R.L. and Najarian, J.S.: Hepatocellular Transplantation in UDP-Glucuronyl Transferase Deficient Rats. Surg. Forum 26:428-431, 1975. Matas, A.J., Sutherland, D.E.R. Steffes, M.W., Lowe, A., Mauer, S.M., Simmons, R.L. and Najarian, J.S.: Hepatocellular Transplantation for Metabolic Deficiencies: Decrease of Plasma Bilirubin in Transplanted Gunn Rats. Science 192:892-894, 1976.